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Reverse T3 in patients with hypothyroidism on different thyroid hormone replacement.
Julian B Wilson1, Thanh D Hoang2, Martin L Lee1,3
1Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, United States of America.
Plos One
|June 9, 2025
Summary
Elevated reverse T3 (rT3) is common in hypothyroid patients on L-T4 therapy. Patients on L-T4 alone showed the highest rT3 levels, suggesting potential issues with this treatment approach.
Area of Science:
- Endocrinology
- Thyroid Hormone Replacement Therapy
Background:
- Reverse T3 (rT3) is an inactive thyroid hormone metabolite.
- Elevated rT3 may impede active T3 binding to receptors.
- Persistent fatigue in patients on L-T4 therapy warrants investigation into alternative explanations.
Purpose of the Study:
- To investigate the prevalence of elevated rT3 in hypothyroid patients with persistent fatigue.
- To compare rT3 levels across different thyroid hormone replacement therapies.
Main Methods:
- Retrospective analysis of 976 patients with hypothyroidism and fatigue.
- Measurement of rT3, TSH, free T3, and free T4.
- LC/MS-MS for rT3 and ECLIA for other hormones.
Main Results:
- 20.9% of patients on L-T4 alone had elevated rT3.
- Patients on L-T4 therapy exhibited higher rT3 levels than those not on replacement (p < 0.00001).
- rT3 levels correlated with free T4 and free T3, and inversely with TSH.
Conclusions:
- Elevated rT3 is observed in hypothyroid patients experiencing fatigue, particularly those on L-T4 monotherapy.
- L-T4 replacement alone was associated with the highest rT3 levels.
- Preparations containing L-T3 showed the lowest rT3 levels.
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